Cosmetic and/or pharmaceutical composition comprising as an active principle at least one peptide and use of this peptide

ABSTRACT

A cosmetic and/or pharmaceutical composition contains, as an active ingredient, at least one peptide from SEQ ID No1 to SEQ ID No8. The use of this peptide as an active ingredient for preparing compositions for inducing, increasing or restoring melanin synthesis in melanocytes of the skin or dermal papilla is also disclosed.

The present invention is in the cosmetic and pharmaceutical domain, andmore particularly in the domain of dermatology. The present inventionconcerns a cosmetic and/or pharmaceutical and/or dermatologicalcomposition containing, as an active principle, at least one peptide ofSEQ ID No. 1 to SEQ ID No. 8.

The active principle according to the invention is designed to induce,increase, or restore the synthesis of melanin in the melanocytes of theepidermis or pilar bulb, with a view to giving the skin a bronzedappearance, to preparing it for exposure to the sun, or to protecting itfrom ultraviolet (UV) radiation. The active principle can also be usedfor therapeutic ends, to prepare pharmaceutical compositions designed torepigment skin depigmented, for example, in the case of vitiligo or topigment fur or hair, in particular in the treatment and the preventionof canities.

In the human being, the color of the hair and of the skin is linked toindividual factors (ethnic origin, sex, age, etc.) and to environmentalfactors (particularly, the seasons of the year, the zone of habitation,etc.) It is principally determined by nature and the concentration ofmelanin produced by the melanocytes. Melanin has the property ofprotecting the cutaneous cells from the deleterious effects of UVradiation and of slowing down cutaneous photo-aging. The melanocytes arespecialized cells which, by the intermediary of specific organelles, themelanosomes, synthesize melanin. The synthesis of melanin, ormelanogensis, is a complex process whose precise mechanisms are stillnot fully clarified and which causes the following stages, representedschematically, to occur:

Tyrosine- ->DOPA- ->Dopaquinone- ->Dopachrome- ->Melanin

In the epidermis, the melanocyte is involved in the epidermal melanicunit that includes one melanocyte surrounded by about 40 neighboringkeratinocytes. As melanin is synthesized in the melanosomes, these aredisplaced from the perinuclear region toward the end of the melanocytedendrites. Through phagocytosis, the end of the dendrites is captured bythe keratinocytes, the membranes damaged, and the melanosomesredistributed in the keratinocytes, where they will provide protectionup until the natural desquamation of the cells. The production ofmelanin, as well as its transport, is regulated by various factors suchas, for instance, UV radiation, hormones, or chemical products. Thus, anincrease in exposure to UV radiation causes the synthesis of pigmentsand the tanning of the skin, which has the effect of protecting the skinfrom UV radiation.

The natural pigmentation of hair and fur by melanin requires thepresence of melanocytes at the level of the bulb of the hair follicle.The hair follicle is a tubular invagination of the epidermis which isembedded as far as the deep layers of the dermis. The melanocytes at thelevel of the hair-follicle bulb are in an active state, that is, theysynthesize melanin. These pigments are conveyed to keratinocytesdestined to form the pilar stem, which will lead to the growth of apigmented hair or fur.

It is accepted that canities (natural whitening of the hair) isassociated with a reduction in melanin in the pilar stem.

The search for compounds able to promote the synthesis of melanin in theskin and the hair in the absence of UV stimulation is a concern ofdermatology and cosmetics. These new compounds would be particularlyuseful as an alternative to exposure to the sun, to prepare the skin andprotect it from the sun's rays, to obtaining a more intense tanningafter exposure to the sun, in prolong the natural pigmentation of theskin after exposure to the sun, or to prevent and/or limit and/or stopthe development of canities and even maintain natural pigmentation ingrey or white hair and/or fur.

Natural pigmentation of the skin is understood to be the coloration ofthe skin or the hair determined by the concentration of melanin.

Fur or hair is understood to be the collection of pilar appendages andparticularly the eyelashes and eyebrows.

In this respect, numerous solutions have been proposed, by introducingexogenous colorants, the best known of which is dihydroxyacetone or DHA.However, only the stimulation of the pigmentation of the skin and/or thehair by natural means permits real protection with respect to UVradiation, and it remains the ideal way to stimulate pigmentation. Thus,the preparation and use of melanin-biosynthesis activators have beenproposed in prior art (FR 828097, FR 2831438, FR 2845285), which causehormones (alpha melanocyte-stimulating hormone (α-MSH) or itsderivatives, WO 2006037188) or prostaglandins (WO 9511003) to intervene.

On the other hand, the use of compounds promoting the synthesis ofmelanin in the skin and hair is very particularly interesting intreating the pathologies causing localized under-pigmentations oforigins which are genetic, autoimmune like vitiligo, due to aging, oreven to post-lesional (scars, mycoses).

The principal objective of the present invention is to provide a newactive principle capable of inducing, increasing, or restoring melaninsynthesis in the melanocytes of the epidermis and the pilar bulb. Theinventors have indeed highlighted the fact that peptides of sequencesSEQ ID No. 1 to No. 8 have remarkable properties, and particularly thatthese peptides, when they are applied to the skin, promote in asignificant way the synthesis of melanin in the melanocytes of theepidermis or of the pilar bulb. These new active principles thus enablenew therapeutic and cosmetic perspectives to be opened up.

Thus, the invention has, as a first object, the use of peptides of thefollowing sequences:

(SEQ ID NO: 1) Asn-Gly-Trp-Lys-Ile-Glu-Arg-Lys (SEQ ID NO: 2)Asn-Gly-Trp-Arg-Val-Asp (SEQ ID NO: 3) Trp-Arg-Leu-Asp-Arg-Lys(SEQ ID NO: 4) Trp-Lys-Leu-Asp (SEQ ID NO: 5) Trp-Arg-Val-Glu(SEQ ID NO: 6) Trp-His-Leu-Glu (SEQ ID NO: 7) Trp-Arg-Ala-Asp(SEQ ID NO: 8) Trp-Lys-Ile-Asp

According to one particularly interesting embodiment, the active peptidecorresponds to the sequence SEQ ID No. 4.

According to another particularly interesting embodiment, the activepeptide corresponds to the sequence SEQ ID No. 5.

The invention also concerns variant forms of these peptide sequences.The term “variant” here refers to a peptide that differs, for example,from the sequence of a reference peptide while still retaining itsessential properties. Generally, the differences are limited in such away that the sequences of the reference peptide and those of the variantare quite similar and, in some regions, identical.

Preferentially, the variant forms are those which vary from thereference sequences by the substitution of chemically equivalent aminoacids (or homologues), that is, by the substitution of one residue byanother one possessing the same characteristics. Thus, the classicsubstitutions are between Ala, Val, Leu, and Ile; between Ser and Thr,between the acidic Asp and Glu residues, between Asn and Gln, andbetween the basic Lys and Arg residues, or between the aromatic Phe andTyr residues. The term “variant” thus refers to a peptide that differs,for instance, in sequence from the reference peptide while stillretaining its essential properties. Generally, the differences arelimited in such a way that the sequences of the reference peptide andthose of the variant are quite similar and, in some regions, identical.A variant peptide and a reference peptide may thus differ in thesequence of amino acids by one or several substitutions, additions, ordeletions in any combination.

The use of a peptide described in the present invention also includesthe use of their variants.

The expression “biologically active” is understood to be “whichpossesses an in vivo or in vitro activity characteristic of the activityof the compound according to the invention”, that is, the property ofinducing, increasing, or restoring the synthesis of melanin inmelanocytes.

Thus, a variant peptide according to the invention will be obtained byone or several substitutions of chemically equivalent amino acids andwill exhibit the property of inducing, increasing, or restoring thesynthesis of melanin in the melanocytes, with an effectiveness similarto that of a peptide of SEQ ID No. 1 to SEQ ID No. 8.

In the invention, the term “amino acid” refers here to any natural ornon-natural organic acid having the formula:—NHR—CR—C(O)—O—where each —R is selected independently from a hydrogen and an alkylgroup having between 1 and 12 carbon atoms. Preferentially, at least onegroup —R of each amino acid is a hydrogen. The term “alkyl” isunderstood here to be a carbon chain which can be linear or branched,substituted (mono- or poly-) or non-substituted; saturated,mono-saturated (a double or triple bond in the chain) orpoly-unsaturated (two or several double bonds, two or several triplebonds, one or several double bonds and one or several triple bonds inthe chain).

The term “peptide” means a chain of two or several amino acids linked toeach other by peptide bonds or by modified peptide bonds. A “peptide” isto be understood as the natural or synthetic peptide of the invention asdescribed above or at least one of its fragments, which might beobtained by proteolysis or synthetically, or even any natural orsynthetic peptide whose sequence is wholly or partially composed of thesequence of the peptide described previously.

So as to improve resistance to damage, it may be necessary to use aprotected form of the peptide according to the invention. The form ofprotection should of course be a biologically compatible form and shouldbe compatible with a use in the domain of cosmetics or pharmaceuticals.

Numerous forms of biologically compatible protection may be envisioned;they are well known to the professional person, such as, for example,the acylation or the acetylation of the amino-terminal end or theamidation or the esterification of the carboxy-terminal end. Thus, theinvention concerns a use as defined previously characterized by the factthat the peptide is in a protected form or not. Preferably, protectionis used which is based either on the acylation or the acetylation of theamino-terminal end, or on the amidation or the esterification of thecarboxy-terminal end, or even on both of these two. The amino acidderivatives and the peptide derivatives also concern amino acids andpeptides connected to one another by a pseudo-peptide bond. A“pseudo-peptide bond” is understood to be any of the types of bondlikely to replace the “classic” peptide bonds.

In the domain of the amino acids, the geometry of the molecules is suchthat they can theoretically exhibit the form of different opticalisomers. Indeed, there exists one molecular conformation of the aminoacid (AA) such that it deflects the plane of light polarization to theright (dextrorotatory or D-aa conformation), and there is anothermolecular conformation of the amino acid (aa) such that it deflects theplane of light polarization to the left (levorotatory or L-aaconformation). In nature, only the levorotatory conformation is retainedin natural amino acids. Consequently, a peptide of natural origin willonly be composed of amino acids of the L-aa type. However, chemicalsynthesis in the laboratory enables amino acids to be prepared whichhave both possible conformations. Starting with this material as a base,it is thus possible during peptide synthesis to incorporate equally wellamino acids in the form of dextrorotatory optical isomers orlevorotatory. Thus, the amino acids composing the peptide according tothe invention may be in the L or D configuration; preferentially, theamino acids are in the L form. The peptide according to the inventioncan thus be in an L, D, or DL form.

The peptide, the object of the present patent, can be obtained either byclassical chemical synthesis (in solid phase or homogeneous liquidphase) or by enzymatic synthesis (Kullman et al. (1980), J. Biol. Chem.225, 8234), starting from the constituent amino acids or theirderivatives.

The peptide according to the invention can also be obtained byfermentation of a strain of bacteria, modified or not by geneticengineering to produce peptides with sequences of SEQ ID No. 1 to No. 8,or even by extraction of proteins of animal or vegetable origin,preferentially of vegetable origin, followed by a controlled hydrolysis,which liberates the peptide fragments of moderate and small size, theobject of the invention.

A great many proteins found in plants are likely to contain thesesequences within their structure. Controlled hydrolysis enables thesepeptide fragments to be released. It is possible, but not necessary toachieve the invention, either to extract the proteins concerned firstand then to hydrolyze them, or to perform the hydrolysis first on a rawextract and to subsequently purify the peptide fragments. It is alsopossible to use certain hydrolyzed extracts without purifying thepeptide fragments in them according to the invention, but while ensuringat the same time the presence of the said fragments by appropriateanalytical means.

Other procedures, simpler or more complex, may be envisioned by theprofessional familiar with the craft of the synthesis, extraction, andpurification of proteins and peptides. Thus, the peptide according tothe invention can be of natural or synthetic origin. Preferentially,according to the invention, the peptide is obtained by chemicalsynthesis.

In the composition according to the invention, the peptides can be amixture of peptide derivatives and/or composed of amino acidderivatives.

According to one advantageous embodiment of the invention, the peptideswith sequences SEQ ID No. 1 to No. 8 are solubilized in advance in oneor several cosmetically or pharmaceutically acceptable solventstraditionally used by the professional, such as water, glycerol,ethanol, propylene glycol, butylene glycol, dipropylene glycol,ethoxylated or propoxylated diglycols, cyclic polyols, vaseline, avegetable oil, or any mixture of these solvents.

According to yet another advantageous embodiment of the invention, thepeptides of sequences SEQ ID No. 1 to No. 8 are solubilized in advancein a cosmetic or pharmaceutical vehicle like the liposomes or areadsorbed onto powdered organic polymers or mineral supports like thetalcs and bentonites, and are more generally solubilized in, or fixedupon, any cosmetically or pharmaceutically acceptable vehicle.

In the composition according to the invention, the peptide can be amixture of peptide derivatives and/or composed of amino acidderivatives. Naturally, the peptide according to the invention can beused alone or in association with at least one other active principle.

The compositions according to the invention can be applied in anyappropriate way, particularly oral, parenteral, or external topical, andtheir formulation will be adapted by the professional, specifically forcosmetic or dermatological compositions. Advantageously, thecompositions according to the invention are intended for administrationby a topical cutaneous means. They contain a physiologically acceptablemedium, a medium acceptable, specifically cosmetologically orpharmaceutically, and particularly dermatologically, and cover allcosmetic or dermatological forms. These compositions should thereforecontain a cosmetically and/or dermatologically acceptable medium, thatis, one compatible with the skin, the fur, or the hair. Thesecompositions can particularly be in the form of creams, oil-in-water orwater-in-oil emulsions, or multiple emulsions, solutions, suspensions,gels, milks, lotions, sticks, or even powders, adapted to an applicationonto the skin, the lips, and/or the hair.

These compositions include the excipients necessary for theirformulation, such as solvents, thickeners, diluents, surfactants,antioxidants, colorants, preservatives, or perfumes.

Of course, the professional will take care to choose possible furthercompounds, active or inactive, and/or their quantity, in such a way thatthe advantageous properties of the mixture are not, or are notessentially, altered by the addition envisioned.

The composition usable according to the invention can, in particular,consist of a composition for hair care, and particularly a shampoo, aconditioner, a blow-dry lotion, a treatment lotion, a cream or a stylinggel, a restructuring lotion for the hair, a mask, etc. The cosmeticcomposition according to the invention can be used particularly intreatments implementing an application that is followed or not by arinse, or even in the form of shampoo.

It can also come in the form of a dye or mascara to be applied with thebrush or the comb, in particular on the eyelashes, eyebrows, or hair.

Naturally, the peptide according to the invention can be used, as anactive principle, alone or even in association with at least one otheractive principle, in a cosmetic composition or for the preparation of adermatological and/or pharmaceutical composition. Advantageously, thecompositions usable according to the invention contain in addition atleast one other compound promoting the pigmentation of the skin, hair,and/or fur.

Such compounds are, particularly, substrates of tyrosinase, such astyrosine or L-DOPA, prostaglandins, or activator compounds by the routeof cyclic adenosine 3′,5′-monophosphate (cAMP) such aspro-opiomelanocortin derivatives, adenosine, or forskolin or itsderivatives. Plant extracts may also be cited, such as the Sevilleorange (Citrus aurantium) or the chrysanthemum (Chrysanthemummorifolium), described particularly in the patents FR 2845285 and EP1014934.

Such compounds are also found in the family of exogenous colorants ofthe surface layers of the epidermis, such as dihydroxyacetone (DHA),erythrulose, and the extracts of henna leaves, described particularly inthe patents EP 0742002 and FR 2779958.

It is quite obvious that the invention is directed toward mammals ingeneral and more particularly toward human beings.

The effective amount of active principle corresponds to the quantitynecessary to obtain the desired result. According to an advantageousembodiment of the invention, the aforementioned peptide is present inthe compositions of the invention in a concentration approximatelybetween 0.0005 and 500 ppm (parts per million), and preferentially in aconcentration approximately between 0.01 and 5 ppm, relative to thetotal weight of the final composition.

These compositions can come particularly in the form of an aqueous,hydroalcoholic, or oily solution, an oil-in-water or water-in-oilemulsion, or multiple emulsions. They can also come in the form ofcreams, suspensions, or even powders, adapted to an application onto theskin, the mucous membranes, the lips, and/or the appendages of the skin.These compositions can be more or less fluid and have the appearance ofa cream, a lotion, a milk, a butter, an ointment, a gel, a paste, or amousse. They can also come in solid form like a stick or be applied onthe skin in the form of an aerosol. They can be used as a care productand/or as a makeup product for the skin.

These compositions include, in addition, any additive commonly used inthe application domain envisioned as well as the adjuvants necessary fortheir formulation, such as solvents, thickeners, diluents, antioxidants,colorants, solar filters, self-tanning compounds, pigments, vehicles,preservatives, perfumes, odor absorbents, active cosmetic orpharmaceutical components, essential oils, vitamins, essential fattyacids, surfactants, film-forming polymers, etc.

In any case, the professional will take care that these adjuvants, aswell as their proportions, are chosen in such a way as not to harm theadvantageous properties studied in the composition according to theinvention. These adjuvants can, for instance, correspond to 0.01 to 30%of the total weight of the composition. When the composition of theinvention is an emulsion, the fatty phase can represent 5 to 80% byweight and preferably 5 to 50% by weight relative to the total weight ofthe composition. The emulsifiers and co-emulsifiers used in thecomposition will be chosen from among those traditionally used in thedomain considered. For example, they can be used in a proportion from0.3 to 20% by weight compared with the total weight of the composition.

Another object of the invention consists of a cosmetic or dermatologicalcomposition characterized by the fact that it contains the compound, ina cosmetically or dermatologically acceptable medium, in order toprepare the skin for exposure to the sun and to protect it from solarradiation.

The invention consists, once again, of a pharmaceutical compositioncharacterized by the fact that the compound is formulated to alleviate apathology linked to pigmentation such as vitiligo which is manifested bya localized under-pigmentation of the skin.

The invention also has, as an object, use in a cosmetic composition orfor preparing a pharmaceutical composition with an effective quantity ofactive principle as described previously, that is, one or severalpeptides of sequence SEQ ID No. 1 to SEQ ID No. 8.

According to a particularly advantageous embodiment, the compositioncontaining it according to the invention contains the peptide withsequence SEQ ID No. 4.

According to another particularly advantageous embodiment, thecomposition according to the invention contains the peptide withsequence SEQ ID No. 5.

The invention also has, as an object, use in a cosmetic composition orfor preparing a pharmaceutical composition with an effective quantity ofactive principle as described previously, the active principle or thecomposition containing it being designed to induce, restore, orstimulate the natural pigmentation of the skin, fur, or hair.

The invention again is related to use in a cosmetic composition or forpreparing a pharmaceutical composition with an effective quantity ofactive principle as described previously, the active principle or thecomposition containing it being designed to prepare the skin forexposure to the sun.

The invention again is related to use in a cosmetic composition or forpreparing a pharmaceutical composition with an effective quantity ofactive principle as described previously, the active principle or thecomposition containing it being designed, by increasing the synthesis ofmelanin, to protect the skin from solar radiation.

The invention again is related to use in a cosmetic composition, or forpreparing a pharmaceutical composition with an effective quantity ofactive principle as described previously, the active principle or thecomposition containing it being designed to improve the intensity and/orthe homogeneity and/or the durability of the pigmentation of the skinand/or of the hair.

The invention has, in addition, as an object, use in a cosmeticcomposition or for preparing a pharmaceutical composition, with aneffective quantity of active principle as described previously, theactive principle or the composition containing it being designed toprotect the skin and its appendages from stresses that the environmentproduces upon them. More precisely, the present invention aims for theuse of at least one active principle as defined previously to protectthe skin and/or its appendages against all types of external aggression.The term “external aggression” is understood to mean aggressions thatthe environment generates. These aggressions may be of chemical,physical, biological, or thermal origin. By way of example, aggressionsby such means as pollution, UV radiation, friction, hard water,variations in temperature, or even products of an irritant nature suchas surfactants, preservatives, and perfumes, may be cited.

Appendages of the skin are understood to be the collection oftegumentary appendages and particularly the nails, the fur, and thehair. Fur and hair are understood to be the assemblage of pilarappendages, and in particular the eyelashes and eyebrows as well.

In addition, the peptides according to the invention, or the compositioncontaining them, have anti-inflammatory and anti-irritant effects. Theuse of the properties of this active principle therefore allows skin tobe more protected and clearly less sensitive to various aggressions thatit may encounter. The skin is thus soothed.

The peptides corresponding to the sequences SEQ ID No. 1 to No. 8 arethus used to fabricate a pharmaceutical composition for topical usage.They will be used in a more general way to treat the dermatologicalconditions linked to pigmentation. In this relation, pathologies likevitiligo may be cited, which is an auto-immune disease characterized bythe appearance on the skin of white patches linked to a pigmentationdeficiency or even to pityriasis versicolor, a surficial mycosis causingthe appearance of light spots which may appear immediately upon or afterexposure to the sun, or even certain pathologies associated withchronologic or actinic aging.

Thus, in another embodiment, the peptides according to the invention, asdescribed previously, can be used to fabricate a medication intended forthe treatment of dermatological conditions.

In another embodiment, the present invention concerns a cosmeticprocedure for increasing the synthesis of melanin in the melanocytes andpromoting the natural pigmentation of the skin and the hair, consistingof applying on the skin or the hair an effective quantity of activeprinciple or of the cosmetic composition containing it, as definedpreviously, in order to obtain the desired action.

The invention also concerns a cosmetic-treatment procedure designed toprevent or to treating the whitening of hair and fur, consisting ofapplying, on the skin, the composition as defined previously.

The invention also concerns a cosmetic-treatment procedure for the careof the skin and/or its appendages consisting of applying onto thesurface of the skin an effective quantity of active principle, or of thecosmetic composition containing it, as defined previously, in order toobtain the desired action.

The cosmetic-treatment procedure of the invention can be implementedparticularly by applying the cosmetic compositions as defined aboveaccording to the usual technique for using these compositions, forexample, application of creams, gels, butters, lotions, milks, shampoos,or sunscreen compositions onto the skin or the hair.

Specific embodiments of this procedure for cosmetic treatment alsoresult from the preceding description. Other advantages andcharacteristics of the invention will be more apparent upon reading theexamples given by way of illustration and non-restrictive.

EXAMPLE 1 Ex Vivo Study of the Effect of the Peptide According to theInvention on the Synthesis of Melanin

The aim of this ex vivo study is to highlight the increase inmelanization produced by the peptides according to the invention.

Protocol: Biopsies of human skin 6 mm in diameter are held in an ex vivoculture in the presence of a specific medium (1 g/L DMEM, Ham's F-12,SVF, and antibiotics) on inserts deposited on 6-well plates. Thebiopsies either receive or do not receive two applications daily of thepeptide with sequence SEQ ID No. 4 in a concentration of 1%, startingwith a 50-ppm solution. The duration of the treatment is 48 hours. Thebiopsies are subsequently fixed in 9% formaldehyde and NaCl (150 mM) for10 hours and then enclosed in paraffin. Thin-sections of the skin 3 μmthick are then made, and the melanin is specifically stained by theFontana-Masson technique.Results: The skin sections which did not receive the application of thecompound exhibit a low-intensity coloration. On the other hand, the skinthin-sections which received applications of peptide with sequence SEQID No. 4 exhibit a coloration of clearly increased intensity. Moreover,the melanin is located in the basal layer but is also transported intothe supra-basal layers.Conclusions: The peptide of sequence of SEQ ID No. 4 induces a strongincrease in the synthesis of melanin by the melanocytes and stimulatesthe entire process of melanin distribution in the epidermis.

EXAMPLE 2 Preparation of Compositions

1. Protective Sun Cream

International Nomenclature of Cosmetic Ingredients % by Trade name(INCI) name volume PHASE A Demineralized water Aqua (water) Insufficient quantity Pemulen ® TR-1 Acrylates/C10-30 alkyl 0.40 acrylatecross-polymer Glycerine Glycerin 3.00 Nipastat ® Sodium Sodiummethylparaben (and) 0.15 sodium ethylparaben (and) sodium butylparaben(and) sodium propylparaben (and) sodium isobutylparaben % by Trade nameINCI name volume PHASE B Parsol ® MCX Ethylhexyl methoxycinnamate 7.50Eusolex ® 4360 Benzophenone-3 3.00 Parsol ® 1789 Butylmethoxydibenzoylmethane 2.00 Myritol ® 318 Caprylic/capric triglyceride4.00 Emulgade ® SEV Hydrogenated palm glycerides (and) 5.00 ceteareth-20(and) ceteareth-12 (and) cetearyl alcohol Propylparaben Propylparaben0.15 Nacol ® 16-98 Cetyl alcohol 1.00 PHASE C TEA Triethanolamine 0.20PHASE D Peptide sequence 0.1 ppm SEQ ID No. 4 Perfume Perfume(fragrance) In sufficient quantity Colorant In sufficient quantityThe constituents of phase A and of phase B are heated separately to atemperature between 70° C. and 75° C. Phase B is emulsified in A whilestirring. Phase C is added, at 45° C., while increasing the stirring.Phase D is finally added when the temperature is below 40° C. Cooling iscontinued down to 25° C. with brisk stirring.

2. Self-Tanning Cream

% by Trade name INCI name volume PHASE A Demineralized water Aqua(water) In sufficient quantity Dipropylene glycol Dipropylene glycol2.00 Glycerine Glycerin 2.00 Glydant Plus ® liquid DMDM hydantoin (and)0.40 iodopropynyl butylcarbamate PHASE B Emulgade ® SEV Glycerylstearate (and) 8.00 ceteareth-20/ceteareth -12 (and) cetearyl alcohol(and) cetyl palmitate Lanette ® O Cetearyl alcohol 1.50 Cetiol ® V Decyloleate 5.00 DC [Dow Cyclomethicone 2.00 Corning]  ™200 Cetiol ® SNCetearyl isononanoate 4.00 Isopropyl palmitate Isopropyl palmitate 3.00Myritol ® 318 Caprylic/capric triglyceride 4.00 Tocopheryl acetateTocopheryl acetate 0.50 PHASE C Peptide sequence 5 ppm SEQ ID No. 5PHASE D Demineralized water Aqua (water) 10.00  DihydroxyacetoneDihydroxyacetone 5.00 PHASE E Caramel W 8016 Caramel 0.02 colorantPerfume Perfume (fragrance) In sufficient quantityPhases A and B are heated separately while stirring at 75° C. Thenemulsify phase B into phase A while stirring vigorously. Introduce thepeptides below 40° C. Then introduce phase D, which was solubilized inthe cold in advance. Color and perfume. Adjust the pH as necessary to4-4.5.

3. Self-Tanning Spray

% by Trade name INCI name volume PHASE A Demineralized water Aqua(water) In sufficient quantity Propylene glycol Propylene glycol 5.00Glycerine Glycerin 2.00 Allantoine Allantoin 0.20 PHASE B Keltrol ® RDXanthan gum 0.05 PHASE C Glydant Plus ® liquid DMDM hydantoin (and) 0.40iodopropynyl butylcarbamate PHASE D Peptide sequence 1 ppm SEQ ID No. 4PHASE E Dihydroxyacetone Dihydroxyacetone 5.00 Demineralized water Aqua(water) 10.00  PHASE F Caramel E 105C Caramel In sufficient colorantquantity Perfume Perfume (fragrance) In sufficient quantityPrepare phase A while stirring. Incorporate the xanthan gum graduallyduring dispersant stirring. Phases C and D will be incorporated once thegel has set. Phase E, prepared in advance to the point of perfect DHAdissolution, will then be added. Adjust the pH if necessary to 4-4.5.Color and perfume.

4. After-Sun Milk

% by Trade name INCI name volume PHASE A Montanov ™ L C14-22 alcohols(and) C12-20 3.00 alkyl glucoside Waglinol 2559 Cetearyl isononanoate4.00 Tegosoft ® TN C12-15 alkyl benzoate 3.00 Apricot kernel oil Prunusarmeniaca (apricot) 2.00 kernel oil Avocado oil Persea gratissima(avocado) oil 1.00 Abil ® 350 Dimethicone 1.00 PHASE B Demineralizedwater Aqua (water) In sufficient quantity PHASE C Simulgel ™ EG Sodiumacrylate/acryloyl- 0.4  dimethyl taurate copolymer (and) isohexadecane(and) polysorbate 80 copolymer (and) polysorbate 80 PHASE D Phenonip ®Phenoxyethanol (and) 0.30 methylparaben (and) ethylparaben (and)butylparaben (and) propylparaben (and) isobutylparaben Ethylparaben andpropylparaben and buthylparaben Germall ® 115 Imidazolidinyl urea 0.20PHASE E Peptide sequence 0.5 ppm SEQ ID No. 4Prepare phase A while stirring. Incorporate the xanthan gum graduallywith dispersant stirring. Phases C and D will be incorporated once thegel has set. Phase E, prepared in advance to the point of perfect DHAdissolution, will then be added. Adjust the pH if necessary to 4-4.5.Color and perfume.

1. A cosmetic or pharmaceutical composition, comprising a peptideconsisting of the amino acid sequence selected from the group consistingof: (SEQ ID NO: 1) Asn-Gly-Trp-Lys-Ile-Glu-Arg-Lys, (SEQ ID NO: 2)Asn-Gly-Trp-Arg-Val-Asp, (SEQ ID NO: 3) Trp-Arg-Leu-Asp-Arg-Lys,(SEQ ID NO: 4) Trp-Lys-Leu-Asp, (SEQ ID NO: 5) Trp-Arg-Val-Glu,(SEQ ID NO: 6) Trp-His-Leu-Glu, (SEQ ID NO: 7) Trp-Arg-Ala-Asp and(SEQ ID NO: 8) Trp-Lys-Ile-Asp,

in a physiologically acceptable medium.
 2. The composition according toclaim 1, wherein said peptide consists of SEQ ID NO:
 4. 3. Thecomposition according to claim 1, wherein said peptide consists of SEQID NO:
 5. 4. The composition according to claim 1, wherein at least onefunctional group of said peptide is protected by a protector group, theprotector group being either an acylation or an acetylation of anamino-terminal end, or an amidation or an esterification of acarboxy-terminal end, or both.
 5. The composition according to claim 1,wherein said peptide is solubilized in advance in one or severalcosmetically or pharmaceutically acceptable solvents.
 6. The compositionaccording to claim 1, wherein said peptide is present in the compositionin a concentration approximately between 0.0005 and 500 ppm.
 7. Thecomposition according to claim 1, in a form adapted for topicalapplication, the composition comprising a cosmetically ordermatologically acceptable medium.
 8. The composition according toclaim 1, wherein said peptide is present in the composition as an activeprinciple, alone or in association with at least one other activeprinciple.
 9. The composition according to claim 1, further comprisingat least one colorant exogenous to surface layers of the epidermisand/or at least one active pro-pigmenting principle different from saidpeptide, selected from substrates of tyrosinase, prostaglandins, cAMPactivator compounds, and pigmenting plant extracts.
 10. An isolatedpeptide consisting of the amino acid sequence selected from the groupconsisting of: (SEQ ID NO: 1) Asn-Gly-Trp-Lys-Ile-Glu-Arg-Lys,(SEQ ID NO: 2) Asn-Gly-Trp-Arg-Val-Asp, (SEQ ID NO: 3)Trp-Arg-Leu-Asp-Arg-Lys, (SEQ ID NO: 4) Trp-Lys-Leu-Asp, (SEQ ID NO: 5)Trp-Arg-Val-Glu, (SEQ ID NO: 6) Trp-His-Leu-Glu, (SEQ ID NO: 7)Trp-Arg-Ala-Asp, and (SEQ ID NO: 8) Trp-Lys-Ile-Asp.


11. A method of preparing a cosmetic composition or a pharmaceuticalcomposition, comprising mixing a physiologically acceptable medium withat least one peptide according to claim
 10. 12. A method of stimulatingnatural pigmentation of skin, fur, or hair in a subject, comprisingapplying topically on an area to be treated of the subject a compositionhaving an effective amount of at least one peptide according to claim10.
 13. A cosmetic or pharmaceutical composition to prepare skin for sunexposure or to protect skin from solar radiation, comprising: at leastone active principle designed to prepare the skin for exposure to thesun or to protect the skin from solar radiation; and at least onepeptide according to claim
 10. 14. A composition to protect skin againstany type of external aggression, comprising at least one peptideaccording to claim
 10. 15. A pharmaceutical composition to alleviatevitiligo, comprising: a pharmaceutically acceptable medium; and at leastone peptide according to claim
 10. 16. A composition to inhibit or totreat whitening of fur and/or hair, comprising: at least one compoundthat promotes pigmentation of the fur or hair; and at least one peptideaccording to claim
 10. 17. A method of increasing synthesis of melaninby melanocytes and stimulating a process of melanin distribution inepidermis in a subject, comprising applying topically on an area to betreated of the subject an effective amount of at least one peptideaccording to claim
 10. 18. The composition according to claim 5, whereinsaid one or several cosmetically or pharmaceutically acceptable solventsare selected from the group consisting of water, glycerol, ethanol,propylene glycol, butylene glycol, dipropylene glycol, ethoxylated orpropoxylated diglycols, cyclic polyols, vaseline, vegetable oil, and anymixture of these solvents.
 19. The composition according to claim 1,wherein said peptide is present in the composition in a concentrationbetween 0.01 ppm and 5 ppm.